tbuckley/cabot-search huggingface dataset:
Abstract 11522: Impact of Chronic Glucagon-Like Peptide-1 Receptor Agonist and Sodium Glucose Cotransporter-2 Inhibitor Therapy on In-Hospital Outcomes of Patients Hospitalized With Acute Myocardial Infarction
Authors: Filippo Trombara, Nicola Cosentino, Stefano Genovese, alice Bonomi, monica ludergnani, Paolo Poggio, Piergiuseppe Agostoni, Giancarlo Marenzi
Journal: Circulation (2022)

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection in addition to their glucose-lowering effect. Whether their benefits occur also in patients with diabetes mellitus (DM) during hospitalization with acute myocardial infarction (AMI) has not been investigated yet. Methods: We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use (before hospitalization) of GLP-1 RA and SGLT-2i therapy. Using administrative healthcare databases, we analyzed patients hospitalized with a primary diagnosis of AMI from 2010 to 2019 in the Lombardy region, Italy. Patients were stratified according to their DM status, then divided into three cohorts: Group 1 (non-DM patients); Group 2 (DM patients taking GLP-1 RA or SGLT-2i); and Group 3 (DM patients not taking GLP-1 RA and/or SGLT-2i). Patients were matched in a 1:1:1 ratio using a propensity score including all available variables. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy. Results: We identified 146,800 patients hospitalized with AMI (26% of them with DM). After propensity score matching, 1,030 patients were included in each group. The primary endpoint rate in the overall population was 16% (n=502) and it significantly increased going from Group 1 to Group 3 (13%, 16%, and 20% respectively; p for trend &amp;lt0.0001). The risk of the composite endpoint significantly increased from Group 1 to Group 3 (P for trend &amp;lt0.0001). In comparison with Group 2, Group 3 had a significant higher risk of the composite endpoint (OR 1.40 [95% CI 1.11-1.77]). Conclusions: Our study shows that DM patients hospitalized with AMI and on chronic GLP-1 RA and/or SGLT-2i therapy have a better in-hospital clinical outcome than DM patients without them.
Abstract 12335: Increasing Awareness About Appropriate High Sensitivity Troponin Use in the Acute Care Setting: Is a Web Based Training Interface the Solution?
Authors: Umair Ansari, Jordan Daloya, rohan perera
Journal: Circulation (2022)

Introduction: High sensitivity troponin (hs-cTnT and hs-cTnI) aimed to reduce costs, observation times and hospital stays. However, since their implementation in many hospital systems across the US many healthcare professionals still struggle in regards to their appropriate utility and interpretation. Hypothesis: We assessed the hypothesis that a web-based training interface is an effective tool to increase education about the proper utility and interpretation of High sensitivity troponin in an acute care setting. Methodology: A web-based training interface was designed with 2 pre-education questions, a slide show based on the 2021 guidelines for chest pain (ie ordering troponin based on presentation, 0+1/2/3 hour) and 2 post-education questions. This interface was sent out to healthcare professionals in a community hospital through email bursts and QR codes. 52 providers participated in the training interface: Internal Medicine residents (n=24), Hospital medicine attendings (n=13), Cardiology Attendings (n=3), Emergency medicine attendings (n=3) and Advanced practice providers (APPs), included nurse practioners and physician assistants (n=9). We measured change in awareness of appropriate and inappropriate troponin use. Fisher's exact test was performed to compare all subgroups. P value &lt;0.05 was considered significant. Results: Our study showed that a web-based training interface increased awareness in the proper usage of high sensitivity troponin across all provider subgroups, with statistically significant results seen among APPs and Resident physicians [Figure]. Conclusion: In conclusion, web-based training applications are a good tool to use when providing information to large numbers of people about high yield topics such as the proper use of and interpretation of High sensitivity troponin and can increase awareness when used appropriately.
Abstract 11374: Aspirin for Primary Prevention of Cardiovascular Events in Patients With Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis
Authors: Harpreet S Bhatia, Patrick Trainor, Samantha Carlisle, Michael Y Tsai, Michael H Criqui, Andrew P Defilippis, Sotirios Tsimikas
Journal: Circulation (2022)

Introduction: There is a lack of effective therapies for reducing risk in people with elevated Lp(a), especially for primary prevention. We aimed to evaluate the association between aspirin use and cardiovascular events (CVD) in people with elevated Lp(a). Methods: We performed a prospective cohort study using data from participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of baseline cardiovascular disease. We matched aspirin users and non-users using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, non-fatal myocardial infarction) stratified by baseline Lp(a) level (above and below 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. Results: Our study cohort included 6,632 participants, including 1,138 (20%) with Lp(a) &gt;50 mg/dL and 1,592 (24%) with baseline aspirin use. Participants with elevated Lp(a) had a higher burden of CVD risk factors, with a trend toward greater aspirin use (25.7% vs 23.6%, p=0.10) and significantly higher CHD events (9.0% vs 7.3%, p=0.03). After propensity matching, aspirin was associated with a significant reduction in CHD events among those with elevated Lp(a) (HR 0.54, 95% CI 0.32-0.94, p=0.03). Those with Lp(a) &gt;50 mg/dL with aspirin use had similar freedom from CHD as those with Lp(a) ≤50 mg/dL regardless of aspirin use ( Figure ). Conclusions: Aspirin use was associated with a significant reduction in CHD events in participants with elevated Lp(a) without baseline CVD. These results are hypothesis generating and require confirmation in studies with randomization of aspirin use.
Abstract 11926: Selective Inhibition of Rho Kinase 2 Limits No Re-Flow in Rat Hearts Following Ischemia/Reperfusion
Authors: Lucie Pearce, David He, Sean M Davidson, Derek M Yellon
Journal: Circulation (2022)

Introduction: Myocardial infarction causes several types of injury to the myocardium including lethal cell injury and ‘no-reflow’ (NRF) /microvascular obstruction (MVO). Nonselective Rho Kinase (ROCK1/2) inhibitors such as Fasudil, ameliorate myocardial ischemia/reperfusion (I/R) injury but cause unwanted hypotension. Selective ROCK2 inhibitors (e.g.: KD025) are safe in clinical trials without causing haemodynamic compromise, however they have not been investigated in myocardial I/R. ROCK inhibitors prevent vascular smooth muscle cell (VSMC) contraction; such VSMC contraction/coronary spasm being features of ‘no-reflow’ (NRF) and microvascular obstruction (MVO). At present, there are limited therapies to improve ischemic MVO outcomes, and prognosis is poor. Hypothesis: Using a rat model, we hypothesised that, i) ROCK2 mRNA is expressed in myocardium and coronary vasculature and ii) The selective ROCK2 inhibitor KD025, would reduce infarct size (IS%) and NRF% (MVO) following I/R. Methods: RNA scope in-situ hybridisation was performed with a fluorescent, multiplex assay for ROCK1/2 &amp; VSMC mRNA in myocardium and coronary vasculature. Male SD rats underwent in-vivo myocardial infarction with 30min ischemia, 180min reperfusion. 15min prior to reperfusion, the ROCK inhibitors Fasudil and KD025 or vehicle (DMSO) were administered i.p. For IS%, myocardium was stained with TTC, and regions not perfused with 1.5% Thioflavin S (NRF%), were visualised under UV light. Results: RNAscope confirmed the presence of ROCK2 mRNA within myocardium and VSMC of coronary arteries. Fasudil ( 10mg/kg ) vs control significantly reduced regional IS% ( 30.3 ± 4.4 vs 52.9 ± 3.8 , p=0.02, n=15 ) and area of NRF% ( 12.4 ± 2.8 vs 28.6 ± 2.2 , p=0.001, n=15 ). However, there was significant hypotension;- Mean BP (mmHg) (72±3.9) vs control (84±2.3, p=0.007 ). KD025 ( 100mg/kg) did not reduce IS%, but significantly reduced the area of NRF% vs control ( 18.4 ± 2.8 vs 28.6 ± 2.2, p=0.02, n=14 ) without hypotensive effect. Conclusions: Our results suggest that ROCK2 may be a prospective target in the management of coronary circulation reperfusion injury and ischemic MVO.
Abstract 11451: Myocardial Neprilysin Expression in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: David W Armstrong, Yan Ru Su, Ashish S Shah, Tarek Absi, Deepak K Gupta, Quinn Wells, D. M Brinkley, Lynne W Stevenson, W. David Merryman
Journal: Circulation (2022)

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis, the underlying mechanisms of which remain poorly understood. Neprilysin (NEP) inhibition has been shown to attenuate hypertrophy and fibrosis in animal models of heart failure, and NEP inhibition is an established therapeutic target in dilated and ischemic cardiomyopathy. However, the myocardial expression of NEP in HCM has not been previously reported. Hypothesis: The expression of NEP is increased in patients with obstructive HCM (oHCM). Methods/Results: We analyzed publicly available gene expression data from two independent cohorts that used myectomy samples from patients with oHCM, and healthy unused donor hearts served as controls. Cohort #1 (NCBI GEO accession number GSE36961) included 107 patients with oHCM and 39 controls and used microarray to assess gene expression. Cohort #2 (NCBI GEO accession number GSE160997) included 18 patients with oHCM and 5 controls and used RNA-Seq to assess gene expression. Both cohorts showed NEP gene expression was significantly increased in oHCM compared to controls (P&lt;0.0001 and P&lt;0.001, respectively). We then examined NEP expression in our surgical cohort (#3), which included 40 patients with oHCM and 8 controls. Using qPCR we showed NEP gene expression was significantly elevated in oHCM compared to controls (P&lt;0.001, see Figure 1). Conclusions: Myocardial NEP gene expression is significantly increased in patients with oHCM undergoing septal myectomy. Future studies are needed to determine if increased myocardial NEP gene expression is accompanied by elevated NEP protein expression and/or activity. Furthermore, future studies are required to determine the mechanism of increased NEP, and whether these findings extend to HCM patients who have not progressed to symptomatic obstruction.
Abstract 11600: Characteristics and Outcomes of Statin Use During Pregnancy: A US Real-World Experience
Authors: Jeffrey L Anderson, Viet T Le, Tami L Bair, Brianna Ronnow, Joseph B Muhlestein, Kirk U Knowlton, Heidi T May
Journal: Circulation (2022)

Introduction: Statins traditionally have been contraindicated during pregnancy because of a theoretical risk of teratogenicity. However, emerging evidence to suggest relative safety and potential harm in contraindicating statins in high cardiovascular (CV)-risk pregnancies have led the FDA in 2021 to remove the “Pregnancy Category X” label. This has placed a heavy burden on physician-patient (pt) shared decision making in that statins “should be discontinued in most pregnant patients or consider the ongoing therapeutic needs of the individual pt, particularly those at very high risk for CV events during pregnancy”. Methods: The objective of this study was to describe the current real-world characteristics of pts prescribed a statin during pregnancy and pregnancy outcomes in a large US healthcare system. Pregnant pts taking a statin were identified by a search of the electronic medical records (eMR) of Intermountain Healthcare, a system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada, between 1997 and 2021, and pregnancy outcomes determined electronically. Statin pts were matched 1:10 by age (+/- 1 y) with non-statin pts. Characteristics and outcomes were determined, and adjusted odds ratios (aOR) were calculated. Results: A total of 63 statin-user pregnancies were matched to 630 controls. Stain pts had more co-morbidities and higher baseline lipids (Table 1). Adverse pregnancy outcomes were more frequent in statin users (Table 2A). However, statin use did not contribute significantly to multivariable risk prediction of miscarriage or congenital anomalies although possibly it did to eclampsia/preeclampsia (Table 2B). Conclusions: In a current real-world US experience, pts prescribed statins during pregnancy had more comorbidities and more adverse outcomes, including fetal anomalies. However, after adjustment, statin use did not contribute to multivariable risk prediction of miscarriage or congenital anomalies.
Abstract 12044: Injectable Contraceptive, Medroxyprogesterone Acetate, Produces Erratic Beating Patterns in Patient-Specific Re-Engineered Heart Cells With Type 2 Long QT Syndrome
Authors: Alexa M Pinsky, Xiaozhi Gao, Sahej Bains, Changsung Kim, David J Tester, Michael J Ackerman
Journal: Circulation (2022)

Background: Type 2 long QT syndrome (LQT2) is an inherited arrhythmia syndrome caused by pathogenic variants in the KCNH2 gene which result in QT prolongation and confers susceptibility to arrhythmic syncope/seizures and sudden cardiac arrest/death. Oral progestin-based contraceptives increase the risk of cardiac events in women with LQT2 and we previously reported the case of a LQT2 woman with recurrent cardiac events attributed to the use of the progestin-based contraceptive, Medroxyprogesterone Acetate (“Depo-Provera”, Depo). Objective: To evaluate the arrhythmic-risk of Depo in a LQT2-specific, induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model. Methods: An iPSC-CM line was generated from the previously reported woman (KCNH2-G1006A*fs) as well as a control line. Voltage-sensing dye was used to assess the optical action potential duration (APD) with 10 μM Depo. 3-D erratic beating patterns were then assessed using multiple electrode array (MEA) with Depo and isoproterenol (ISO) to mimic an adrenergic surge. Results: Addition of Depo to the G1006A*fs iPSC-CMs decreased the optical APD from baseline 438±14 ms (n=6) to 363±35 ms (n=12; p=0.0001). Despite the APD shortening at baseline, in the setting of ISO, Depo administration induced erratic beating patterns in MEA, characterized as alternating spike amplitudes, alternans, or early after depolarization-like phenomena. Combined Depo and ISO treatment increased the percent of electrodes displaying erratic beating in G1006A*fs [baseline 8%±13 vs. Depo + ISO 38%±40 (p=0.0097)] but not in controls [baseline 2%±5 vs. Depo + ISO 7%±11 (p=0.14)]. Neither Depo nor ISO alone changed beating patterns in G1006A*fs [baseline 8%±13, Depo 30%±41 (p=0.08), ISO 21%±30, (p=0.17)] and controls [baseline 2%±5, Depo 3%±7 (p=0.61), ISO 0%±0 (p=0.4)]. Conclusion: This patient-specific, re-engineered heart cell study provides a potential mechanism for the patient’s clinically documented, Depo-associated episodes of recurrent ventricular fibrillation. This in-vitro data should prompt a large-scale clinical assessment of Depo’s potential pro-arrhythmic effect in women with LQT2.
Abstract 12315: Prognostic Value of Proteinuria on Cardiac Events in Japanese Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Syuhei Ikeda, Moritake Iguchi, Hisashi Ogawa, Yumiko Nakanishi, Kimihito Minami, Kenjiro Ishigami, KOSUKE DOI, Yasuhiro Hamatani, Takashi Yoshizawa, Yuya Ide, Akiko Fujino, Mitsuru Ishii, Nobutoyo Masunaga, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2022)

Background: Previous studies have suggested that proteinuria is independently associated with incidence of atrial fibrillation (AF). However, data regarding the impact of proteinuria on clinical outcomes in patients with AF are limited. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available in 4,489 patients, and 2,164 patients with available data of proteinuria as the results of the urine test by dipstick were examined. We divided these patients into three groups according to the level of proteinuria; positive group (n=339), trace group (n=267) and negative group (n=1,558). Results: Patients in positive group and trace group were older (positive vs. trace vs. negative; 75.9±9.7 vs. 75.7±10.8 vs. 73.4±10.5; p&lt;0.01), had higher prevalence of heart failure (HF), hypertension, diabetes mellitus and renal dysfunction (estimated glomerular filtration rate &lt;60 ml/min/1.73 m 2 ), and had higher CHADS 2 score (2.6±1.4 vs. 2.5±1.3 vs. 2.0±1.3; p&lt;0.01) and HAS-BLED score (2.2±1.2 vs. 1.9±1.0 vs. 1.7±1.0; p&lt;0.01). During the median follow-up of 2,978 days, the incidence rates of cardiac events (composite of cardiac death or HF hospitalization during follow-up) were higher in patients in both of positive group and trace group than patients in negative group (3.8% vs. 4.0% vs. 1.9% per person-year; p&lt;0.01) (Figure). Multivariate Cox proportional hazards regression analysis revealed that proteinuria was an independent determinant of cardiac events (positive vs. negative; adjusted hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.12-1.85, trace vs. negative; adjusted HR: 1.60, 95% CI: 1.23-2.09). Conclusion: In Japanese patients with AF, the presence of proteinuria, even if it was trace level, was associated with higher incidence of cardiac events.
Abstract 12528: Variants in Solute Cation Transporters 3 Associate with High Lp(a) Levels Independent of Apo(a) Isoform Size
Authors: Lamia Ismail, Michael Black, Michael Williams, Stefan Coassin, Lukas Forer, F. Kronenberg, Sally McCormick
Journal: Circulation (2022)

Introduction: Lipoprotein (a) [Lp(a)] consists of a low-density lipoprotein (LDL) molecule attached to apolipoprotein(a) [apo(a)]. Apo(a) comprises two kringle domains (KIV and KV) derived from the plasminogen gene and an inactive protease domain. The KIV domain is subdivided into 10 subtypes (KIV1-10), with KIV2 occurring as a copy number variation (CNV) that varies among individuals. Elevated Lp(a) levels are a major risk factor for CVDs and are inversely correlated to the KIV2 CNV determining apo(a) isoform size. Objectives: This study aimed to identify variants associated with a high Lp(a) phenotype that were not linked to apo(a) isoform size. Methods: Illumina sequencing of 13 candidate genes was performed on a discovery set comprising 54 high Lp(a) European samples (&gt;50mg/dL). The sequenced genes included LPA, adjacent genes, and those coding for receptors involved in Lp(a) uptake. Variants commonly found in high samples were genotyped in the Otago LPA European cohort (n=589) and their association with Lp(a) levels was checked via Kruskal-Wallis and linear regression statistical models. The associations were then replicated in the much bigger German Chronic Kidney Disease (GCKD) cohort (n=4930). Results: Nine variants were significantly associated with high Lp(a) levels. Two variants were in the LPA gene (rs3124784 and rs3798220) and seven were in neighbouring genes (rs2282143 in SLC22A1, rs3127592, rs3127593, rs3103353 and rs3127594 in SLC22A2 and rs1810126 and rs3088442 in SLC22A3). Interestingly, the minor allele of all nine variants was significantly associated with increased LPA expression in liver tissues in the GTEx database. Seven of the variants were significantly associated with small apo(a) isoform size (P=1x10-4 to 2.9x10-18), while rs1810126 and rs3088442 in SLC22A3 were not associated with the small isoform size (P=0.43 and 0.42). Conclusion: Nine variants in the LPA and nearby genes were significantly associated with elevated Lp(a) levels and increased LPA expression, with the majority being linked to a short apo(a) isoform. The association of two SLC22A3 gene variants with Lp(a) levels independent of apo(a) isoform size warrants further investigation to establish any functional connection between LPA and this gene.
Abstract 11294: Rates of Testing in Syncope Patients in the United States Using a National Database
Authors: Madeline Smoot, Chen Bai, Emily S Edwards, Osama Dasa, John W Petersen, Stephen E Kimmel, Mamoun T Mardini, Mohammed Ruzieh
Journal: Circulation (2022)

Introduction: Syncope is a prevalent health problem. Most causes of syncope are benign and can be diagnosed based on history and physical examinations. Nonetheless, overtesting for syncope is a major healthcare problem associated with increased costs. In this study, we sought to assess the testing trends for the evaluation of syncope. Methods: We used data from the IBM MarketScan Research Database, which captures deidentified, individual-level information in the United States from approximately 100 commercial payers and self-insured corporations, not including Medicaid claims. We identified patients with the first diagnosis of syncope from 2010-2020 using ICD-9 and ICD-10 codes. Patients were followed up for three months to determine the rate of testing for syncope. Results: We identified 2,500,850 patients (57.9% women) with a mean age of 48.5 years. The overall rate of anatomical neurological testing was higher than cardiac anatomical testing (43.3% vs. 25.5%, p&lt;0.001). The rate of the following tests decreased over time: cardiac stress testing (17.4% to 11.4%, p&lt;0.001, figure 1A), carotid ultrasound (13.1% to 7.2%, p&lt;0.001, figure 1C) and EEG (7.3% to 5.7%, p&lt;0.001, figure 1C). The rate of CT chest angiography increased significantly (3.6% to 6.1%, p&lt;0.001, figure 1B). The rates of long-term ECG monitoring, echocardiogram, chest x-ray, and neck and brain imaging remained the same (Figures 1A-C). Conclusion: Although prior studies demonstrated low yield for most cardiac and neurological evaluations for syncope and the reduction of testing over time (stress testing, carotid doppler, EEG), high rates of testing remained prevalent in syncope patients. Efforts are needed to reduce the use of low-yield diagnostic studies in syncope patients.